Your browser doesn't support javascript.
loading
Time-Restricted Feeding Ameliorates Methionine-Choline Deficient Diet-Induced Steatohepatitis in Mice.
Jung, Ik-Rak; Ahima, Rexford S; Kim, Sangwon F.
Affiliation
  • Jung IR; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Ahima RS; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Kim SF; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University, Baltimore, MD 21218, USA.
Int J Mol Sci ; 25(3)2024 Jan 23.
Article in En | MEDLINE | ID: mdl-38338668
ABSTRACT
Non-alcoholic steatohepatitis (NASH) is an inflammatory form of non-alcoholic fatty liver disease (NAFLD), closely associated with disease progression, cirrhosis, liver failure, and hepatocellular carcinoma. Time-restricted feeding (TRF) has been shown to decrease body weight and adiposity and improve metabolic outcomes; however, the effect of TRF on NASH has not yet been fully understood. We had previously reported that inositol polyphosphate multikinase (IPMK) mediates hepatic insulin signaling. Importantly, we have found that TRF increases hepatic IPMK levels. Therefore, we investigated whether there is a causal link between TRF and IPMK in a mouse model of NASH, i.e., methionine- and choline-deficient diet (MCDD)-induced steatohepatitis. Here, we show that TRF alleviated markers of NASH, i.e., reduced hepatic steatosis, liver triglycerides (TG), serum alanine transaminase (ALT) and aspartate aminotransferase (AST), inflammation, and fibrosis in MCDD mice. Interestingly, MCDD led to a significant reduction in IPMK levels, and the deletion of hepatic IPMK exacerbates the NASH phenotype induced by MCDD, accompanied by increased gene expression of pro-inflammatory chemokines. Conversely, TRF restored IPMK levels and significantly reduced gene expression of proinflammatory cytokines and chemokines. Our results demonstrate that TRF attenuates MCDD-induced NASH via IPMK-mediated changes in hepatic steatosis and inflammation.
Subject(s)
Key words

Full text: 1 Database: MEDLINE Main subject: Choline Deficiency / Non-alcoholic Fatty Liver Disease Limits: Animals Language: En Journal: Int J Mol Sci Year: 2024 Type: Article Affiliation country: United States

Full text: 1 Database: MEDLINE Main subject: Choline Deficiency / Non-alcoholic Fatty Liver Disease Limits: Animals Language: En Journal: Int J Mol Sci Year: 2024 Type: Article Affiliation country: United States